Vitamin E analog modulates UVB-induced signaling pathway activation and enhances cell survival

Péus, Dominik; Meves, Alexander; Pott, Markus; Beyerle, Astrid; Pittelkow, Mark R.

doi:10.1016/s0891-5849(00)00488-3

Cited by 31 publications

(21 citation statements)

References 47 publications

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“…Trolox pre-treatment suppressed ROS generation and a significant decrease in peroxide production was detected when the cells were treated with Trolox for 14 h. These results were consistent with the findings of Peus et al , on human keratinocytes, in which Trolox was found to decrease the intracellular H 2 O 2 generation in a dose-dependent manner. [26]…”

Section: Resultsmentioning

confidence: 99%

Intracellular scavenging activity of Trolox (6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid) in the fission yeast, Schizosaccharomyces pombe

et al. 2010

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The ability of Trolox (6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid), a water-soluble vitamin E analogue, to prevent oxidative damages is well characterized, but the mechanisms underlying it remain unclear. The protective effect of Trolox pre-treatment on H2O2-induced toxicity might be attributed to the decreased cellular permeability to H2O2 or in vitro scavenging activity of Trolox, induction of antioxidant enzymes or the direct scavenging activity of Trolox. The results obtained rule out the first and second possibilities and intracellular scavenging activity was found to be the mechanism whereby Trolox confers protection. This was confirmed by measuring protein oxidation (levels), and the observed decrease in proteasomal activity indicated that the decrease in protein carbonyls was due to Trolox scavenging activity rather than proteasome activation. In conclusion, the intracellular scavenging activity of Trolox is a key protective mechanism against H2O2. These findings obtained in Schizosaccharomyces pombe, a good model organism for eukaryotic cells, can be used as standard protocols for investigating the antioxidant activity of pure or complex potential antioxidants.

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Section: Resultsmentioning

confidence: 99%

Intracellular scavenging activity of Trolox (6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid) in the fission yeast, Schizosaccharomyces pombe

et al. 2010

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“…Vitamin E derivatives outrun any destructive interactions of hydroperoxyl radicals with polyunsaturated fatty acids by scavenging these radicals at ~1.000-fold faster kinetics and thereby break lipid peroxidation chain reactions (Buettner, 1993; Traber and Stevens, 2011; Alberto et al, 2013). Furthermore, they also react with singlet oxygen as well as superoxide, and decrease the cell endogenous H 2 O 2 formation (Brigelius-Flohé and Traber, 1999; Peus et al, 2001). Most importantly, vitamin E is not degraded in the scavenging process but is rather “recycled” to its reduced state by, e.g., vitamin C (Buettner, 1993; Traber and Stevens, 2011), which further optimizes its efficiency.…”

Section: Discussionmentioning

confidence: 99%

The free radical scavenger Trolox dampens neuronal hyperexcitability, reinstates synaptic plasticity, and improves hypoxia tolerance in a mouse model of Rett syndrome

Janc

Müller

2014

Front. Cell. Neurosci.

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Rett syndrome (RS) causes severe cognitive impairment, loss of speech, epilepsy, and breathing disturbances with intermittent hypoxia. Also mitochondria are affected; a subunit of respiratory complex III is dysregulated, the inner mitochondrial membrane is leaking protons, and brain ATP levels seem reduced. Our recent assessment of mitochondrial function in MeCP2 (methyl-CpG-binding protein 2)-deficient mouse (Mecp2-/y) hippocampus confirmed early metabolic alterations, an increased oxidative burden, and a more vulnerable cellular redox balance. As these changes may contribute to the manifestation of symptoms and disease progression, we now evaluated whether free radical scavengers are capable of improving neuronal and mitochondrial function in RS. Acute hippocampal slices of adult mice were incubated with the vitamin E derivative Trolox for 3–5 h. In Mecp2-/y slices this treatment dampened neuronal hyperexcitability, improved synaptic short-term plasticity, and fully restored synaptic long-term potentiation (LTP). Furthermore, Trolox specifically attenuated the increased hypoxia susceptibility of Mecp2-/y slices. Also, the anticonvulsive effects of Trolox were assessed, but the severity of 4-aminopyridine provoked seizure-like discharges was not significantly affected. Adverse side effects of Trolox on mitochondria can be excluded, but clear indications for an improvement of mitochondrial function were not found. Since several ion-channels and neurotransmitter receptors are redox modulated, the mitochondrial alterations and the associated oxidative burden may contribute to the neuronal dysfunction in RS. We confirmed in Mecp2-/y hippocampus that Trolox dampens neuronal hyperexcitability, reinstates synaptic plasticity, and improves the hypoxia tolerance. Therefore, radical scavengers are promising compounds for the treatment of neuronal dysfunction in RS and deserve further detailed evaluation.

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“…1). The study of Peus et al (2001) on human keratinocytes treated with Trolox revealed that Trolox inhibits intracellular H 2 O 2 generation in keratinocytes in a concentration-dependent manner. 2).…”

Section: Ros Generation Due To Normal Cellular Metabolismmentioning

confidence: 99%

Prevention of intracellular oxidation in yeast: the role of vitamin E analogue, Trolox (6‐hydroxy‐2,5,7,8‐tetramethylkroman‐2‐carboxyl acid)

Raspor

Plesničar

Gazdag

et al. 2005

Cell Biology International

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Reactive oxygen species (ROS) are not only generated in conditions of cellular stress but are also constitutively produced in most cell types by specific metabolic processes. This research focused on a potential antioxidant Trolox (model compound for alpha-tocopherol), with the aim to establish exact mechanisms of Trolox intracellular oxidation prevention on model organism Saccharomyces cerevisiae. Measuring intracellular oxidation of Trolox-treated yeast cells revealed that Trolox decreased intracellular oxidation during normal metabolism. Trolox treatment decreased cyto- and geno-toxicity of treated yeast cells in MES buffer, lowered intracellular oxidation, decreased intracellular peroxides formation, and increased H(2)O(2) degradation and superoxide quenching yeast extract ability. This study suggests that Trolox treatment provides prevention against intracellular ROS formation. Trolox application as therapeutic agent against intracellular ROS formation would be worth considering. Additionally, results indicate that yeasts are good model organisms for studying intracellular oxidation and oxidative stress. The obtained results on yeast cells might be useful to direct further human-related search for the Trolox evaluation as a human supplement used for protecting cells against intracellular free radical formation.

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Vitamin E analog modulates UVB-induced signaling pathway activation and enhances cell survival

Cited by 31 publications

References 47 publications

Intracellular scavenging activity of Trolox (6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid) in the fission yeast, Schizosaccharomyces pombe

Intracellular scavenging activity of Trolox (6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid) in the fission yeast, Schizosaccharomyces pombe

The free radical scavenger Trolox dampens neuronal hyperexcitability, reinstates synaptic plasticity, and improves hypoxia tolerance in a mouse model of Rett syndrome

Prevention of intracellular oxidation in yeast: the role of vitamin E analogue, Trolox (6‐hydroxy‐2,5,7,8‐tetramethylkroman‐2‐carboxyl acid)

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